Search Results (143)

Background/Objectives: Solvent-intensive methods are traditionally required to extract curcumin, a potent bioactive compound from Curcuma longa, raising environmental and safety concerns. Methods: This study introduces an efficient and scalable extraction approach using microwave–ultrasound-assisted extraction (MUAE) combined with a natural deep eutectic solvent (NADES) composed of choline chloride and lactic acid. Process parameters, including solvent water content (20–30% v/v) and solid loading (4–8% w/v), were optimized using response surface methodology (RSM) to enhance curcumin yield. Results: Under optimal conditions (20% water content and 8% solid loading), the MUAE method achieved a curcumin content of 40.72 ± 1.21 mg/g, representing a 14.36% improvement over conventional ultrasound-assisted extraction (UAE), while reducing solvent usage by 50%. The quadratic model demonstrated excellent predictive capability, with an R² value of 0.98. In addition, anti-solvent precipitation using water increased curcuminoid purity from 0.31% to 20.54%, with a recovery rate of 21.49%. Conclusions: Mechanistic analysis revealed that microwave-induced cell disruption, ultrasound cavitation, and the modulation of NADES viscosity contributed synergistically to the enhanced extraction performance. This study is the first to combine MUAE with NADES for optimized curcumin extraction, delivering both high yield and reduced solvent consumption. The proposed method offers a sustainable and industrially relevant alternative for curcumin recovery in the food, nutraceutical, and pharmaceutical sectors. Full article

Gamma oryzanol (GO) is a natural anti-oxidant found in rice bran with potential health benefits. Conventional isolation of GO from rice bran requires the use of non-eco-friendly solvents such as acetone, ethyl acetate and hexane due to its low aqueous solubility. Further, nanoencapsulation of GO is required for the enhancement of stability and bioavailability. Plant-derived nanovesicles (PDNVs) are natural/intrinsic exosome-mimetic vesicles isolated from edible plants using green methods. Washed/soaked rice water (SRW) is often discarded as waste prior to cooking rice. However, traditional knowledge indicates its health-promoting anti-oxidant benefit, probably contributed by the presence of GO. Herein, for the first time, we isolated PDNVs from SRW by the cost-effective Polyethylene glycol 6000(PEG) precipitation method and demonstrated the presence of GO in PDNVs. In our initial screen, PDNVs were isolated from both rice grains (RGs) as well as the SRW of four different rice varieties, in which we identified the copious presence of GO in black RGs and brown SRW PDNVs. Both RG and SRW PDNVs were non-toxic to keratinocytes. SRW PDNVs displayed distinct cellular uptake mechanisms compared to RG PDNVs in human keratinocytes. Compared to native GO, brown SRW PDNVs containing GO displayed superior anti-oxidant activity in HaCaT keratinocytes, likely due to its enhanced cellular uptake. Overall, we describe here a waste-to-wealth green approach using an economical PEG method for the extraction of GO in bioavailable form. Given that oxidative stress is a driving factor for inflammation and related diseases, SRW PDNVs provide an affordable natural formulation for the treatment of diseases with underlying oxidative stress and inflammation. Full article

The advancement of modern lifestyles has precipitated excessive consumption of energy-dense foods, driving the escalating global burden of lipid metabolism dysregulation-related pathologies—including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disorders—which collectively pose a formidable challenge to global public health systems. The almond hull, as a by-product of almond processing, is rich in polyphenolic compounds with demonstrated antioxidant, anti-inflammatory, and lipid-lowering potential, though its precise hypo-lipidemic mechanisms remain elusive. In this study, polyphenols were extracted from almond hulls using 50% ethanol with ultrasound-assisted extraction, followed by preliminary purification via solvent partitioning. The ethyl acetate fraction was analyzed by liquid chromatography–mass spectrometry (LC-MS). Network pharmacology and molecular docking were employed to investigate the interactions between key bioactive constituents (e.g., quercetin, baicalein, and kaempferol) and targets in lipid metabolism-related pathways. Molecular dynamics (MD) simulations further evaluated the stability of the lowest-energy complexes. Results revealed that the ethyl acetate fraction exhibited potent pancreatic lipase inhibitory activity (IC50 = 204.2 µg/mL). At 0.1 mg/mL after 24 h treatment, it significantly reduced free fatty acids (FFAs)-induced intracellular triglyceride accumulation (p < 0.01) and enhanced cellular antioxidant capacity. Network pharmacology and in vitro studies suggest almond hull extract modulates PI3K-AKT signaling and improves insulin resistance, demonstrating lipid-lowering effects. These findings support its potential in functional foods and pharmaceuticals, though further in vivo validation and mechanistic investigations are required. Full article

Alkaline treatment is well suited for extracting high-molecular-weight hemicelluloses, specifically hardwoods xylans, which, due to their polymer structure and chemical characteristics, enable the production of films with desirable mechanical, barrier, and optical properties for packaging applications. Despite its relevance, the optimization of antisolvent addition has received little attention in the literature. This study explores the use of eucalyptus industrial residue as feedstock, utilizing a statistical design to determine the optimal extraction conditions for hemicelluloses while minimizing the lignin content in the recovered liquor. The process uses alkali loads that are compatible with those in conventional Kraft pulp mills. Optimal extraction conditions involve a temperature of 105 °C, 16.7% NaOH charge, and 45 min at maximum temperature. The resulting liquor was subjected to ethanol precipitation under varying pH conditions (initial pH, 9, 7, 5, and 2) and different ethanol-to-liquor ratios (1:1 to 4:1). The acidification was performed using hydrochloric, sulfuric, and acetic acids. Ethanol served as the main antisolvent, while isopropyl alcohol and dioxane were tested for comparison. Results show that 2.3 ± 0.2% of xylans (based on oven-dry biomass) could be extracted, minimizing lignin content in the liquor. This value corresponds to the extraction of 15.6% of the xylans present in the raw material. The highest xylan precipitation yield (78%) was obtained at pH 7, using hydrochloric acid for pH adjustment and an ethanol-to-liquor ratio of 1:1. These findings provide valuable insight into optimizing hemicellulose recovery through antisolvent precipitation, contributing to more efficient biomass valorization strategies within lignocellulosic biorefineries. Full article

The antisolvent precipitation method was employed to synthesize curcumin-loaded gliadin–carboxymethyl chitosan (CMCS) composite nanoparticles (GCC NPs). When the gliadin/CMCS weight ratio was 2:1, the GCC NPs with an ideal negative charge (−27.57 ± 1.07 mV) and the minimum particle size (184.13 ± 5.49 nm) were obtained. With the addition of CMCS, the encapsulation efficiency (EE) of Cur was markedly improved from 77.46 ± 1.54% to 93.88 ± 1.31%. Under various pH values and salt concentrations, the GCC NPs displayed excellent colloidal stability. Specifically, after encapsulation within the GCC NPs, the antioxidant activity of Cur was markedly improved. In ABTS and DPPH assays, the SC₅₀ values of the GCC NPs were 4.98 ± 0.07 µg/mL and 9.86 ± 0.29 µg/mL, respectively. In summary, the GCC NPs would be an effective platform for the delivery of Cur in food and pharmaceutical preparations. Full article

In this study, an improved method combining natural surfactants with a solvent–antisolvent precipitation technique was developed to prepare highly effective nano-sized tangeretin particles. Various natural surfactants were tested and compared, and the formulation was optimized using Plackett–Burman and Box–Behnken design methodologies. The optimal preparation conditions were identified as follows: a tangeretin–dimethyl sulfoxide (DMSO) solution concentration of 5.23 mg/mL, surfactant concentration of 4.72%, and a rotor diameter of 20 mm. Under these conditions, uniform nano-tangeretin particles with an average size of 428.73 ± 30.25 nm were successfully produced. The preparation process significantly reduced particle size without chemical structure of tangeretin, as confirmed by spectral analysis. Importantly, the free radical scavenging activity of the nano-tangeretin was markedly enhanced, showing 65.4% increase in DPPH radical inhibition compared to the unprocessed powder. These results demonstrate that the proposed method can improve the bioactivity and dispersibility of tangeretin, providing a valuable strategy for the efficient utilization and industrial-scale production of bioactive compounds from natural resources. Full article

Background/Objectives: Natural products are gaining increasing importance due to the large variety of biological activities exerted by their constituents. Among these, the products deriving from Acmella oleracea (L.) R.K. Jansen can be exploited for their local anaesthetic, myorelaxant, anti-inflammatory/analgesic, and antifungal properties. In this regard, there is a need to develop novel formulations for the topical delivery of A. oleracea-derived extracts to widen their use in the pharmaceutical and cosmetic fields. Methods: Nanoformulations, i.e., nanoemulsions (NEs) and microemulsions (MEs), were investigated as a strategy to encapsulate an extract from A. oleracea at the nanoscale level in water and then incorporated into xanthan gum-based hydrogels. Results: Only NEs provided a physically stable formulation, while the precipitation of solid hydrophobic components from the extract was observed during ME preparation under all tested conditions despite the use of ethyl oleate as an oily co-solvent. The optimized NE-based hydrogel remained physically stable over six months, as confirmed by rheological measurements and polarized optical microscope observation, without a phase separation phenomenon. Therefore, NEs resulted more suitable nanodispersed systems than MEs for the encapsulation of A. oleracea extract, which contains a large amount of hydrophobic constituents that are solid at room temperature. Furthermore, the sustained spilanthol release across an artificial membrane (Franz cell apparatus) and the cytotoxic profile on HaCaT cell line support its potential topical application. Conclusions: The outcomes of this study provided valuable insights into the formulation of A. oleracea extract, broadening its fields of applicability, including topical administration. Full article

Zein was made flexible through acid-driven deamidation. This increased flexibility was confirmed by the higher release of water-soluble peptides during trypsin hydrolysis. Self-assembled flexible zein nanoparticles (FZNPs) were prepared using the anti-solvent precipitation method. To test the sensitivity of FZNPs to complex environment, ionic solutions (CaCl₂ and NaCl) at various concentrations were prepared. The morphology and particle size of FZNPs differed significantly from those of control zein nanoparticles (NZNPs). As the ionic concentration increased from 0 to 15 mmol/L, FZNPs showed higher electrical conductivity and adsorption capacity than NZNPs. This suggests that FZNPs are highly sensitive to complex environment. X-Ray Photoelectron Spectrum (XPS) results revealed that both FZNPs and NZNPs bound more Na⁺ than Ca²⁺. The enhanced sensitivity of FZNPs to complex environments may be due to their greater tendency for structural changes. These conformational changes are likely caused by the altered amino acids in flexible zein, which result from deamidation. This study offers a practical approach to designing novel nanoparticles as functional materials for delivering bioactive compounds. Full article

Background/Objectives: The co-formulation of active pharmaceutical ingredients (APIs) is a growing strategy in biopharmaceutical development, particularly when it comes to improving solubility and bioavailability. This study explores a co-precipitation method to prepare co-formulated crystals of griseofulvin (GF) and dexamethasone (DXM), utilizing nanostructured, functionalized polylactic glycolic acid (nfPLGA) as a solubility enhancer. Methods: An antisolvent precipitation technique was employed to incorporate nfPLGA at a 3% concentration into the co-formulated GF and DXM, referred to as DXM-GF-nfPLGA. The dissolution performance of this formulation was compared to that of the pure drugs and the co-precipitated DXM-GF without nfPLGA. Results: Several characterization techniques, including electron microscopy (SEM), RAMAN, FTIR, TGA, and XRD, were used to analyze the nfPLGA incorporation and the co-precipitated co-formulations. The inclusion of nfPLGA significantly enhanced the dissolution and initial dissolution rate of both GF and DXM in the DXM-GF-nfPLGA formulation, achieving a maximum dissolution of 100%, which was not attained by the pure drugs or the DXM-GF formulation. The incorporation of nfPLGA also reduced the amount of time taken to reach 50% (T₅₀) and 80% (T₈₀) dissolution. T₅₀ values decreased from 52 and 82 min (for pure DXM and GF) to 23 min for DXM-GF-nfPLGA, and the T₈₀ improved to 50 min for DXM-GF-nfPLGA, significantly outpacing the pure compounds. Furthermore, incorporating nfPLGA into the crystal structures greatly accelerated the dissolution rates, with initial rates reaching 650.92 µg/min for DXM-GF-nfPLGA compared to 540.60 µg/min for DXM-GF, while pure GF and DXM showed lower rates. Conclusions: This work demonstrates that nfPLGA incorporation enhances dissolution performance by forming water channels within the API crystal via hydrogen-bonding interactions. This innovative nfPLGA incorporation method holds promise for developing hydrophobic co-formulations with faster solubility and dissolution rates. Full article

Antioxidants are contained in fruits and vegetables and are commonly obtained through food. However, it is frequently necessary to supplement the diet with substances that are often poorly soluble in water and sensitive to light and oxygen. For this reason, in this work, luteolin (LUT) and naringenin (NAR), two compounds with antioxidant activity and potential health benefits, were precipitated through the supercritical antisolvent technique using polyvinylpyrrolidone and β-cyclodextrin as the carriers. The precipitation occurred from dimethylsulfoxide using supercritical carbon dioxide as the antisolvent. The influence of pressure (9–12 MPa), active substance/carrier concentration in the solution (20–200 mg/mL), and their ratio (1/1 and 1/2 mol/mol) on morphology, particle mean size, and distribution were investigated. Under the optimized operating conditions, spherical microparticles with a mean diameter equal to 2.7 ± 0.9 μm (for LUT) and 5.5 ± 1.9 μm (for NAR) were obtained. The active ingredients were protected from the external environment by the presence of the carrier, and the dissolution rate was notably increased by processing them with β-cyclodextrin. It was sixty times faster and three times faster than that of the antioxidant alone for LUT and NAR, respectively. Full article

Celecoxib (CEL), a nonsteroidal anti-inflammation drug (NSAID), is categorized as a Class II drug (low solubility, high permeability) in the Biopharmaceutics Classification System (BCS). The aim of this study is to develop a novel formulation of CEL nanosuspensions in the form of dried powder for tableting or capsuling. In this study, CEL was formulated into nanosuspensions to improve its solubility. CEL nanosuspensions were prepared using the precipitation method followed by high-pressure homogenization. Drying of the nanosuspensions was performed by spray drying and freeze drying. We examined the impact of various formulation and processing parameters on the nanoparticles. The CEL nanoparticles were characterized by particle size analysis, differential scanning calorimetry (DSC), powder X-Ray diffraction (PXRD), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and dissolution tests. The choice of solvent, stabilizer, and surfactant appeared to have significant impacts on the crystallization and particle size and, consequently, the solubility of the CEL nanoparticles. CEL chemical stability was maintained throughout both drying processes. Both spray-dried and freeze-dried CEL nanosuspensions showed rapid dissolution profiles compared to raw CEL due to the nanosized particle dispersion with the presence of a lag phase. The freeze-dried nanosuspension showed a slight delay in the first 20 min compared to the spray-dried nanosuspension, after which dissolution progressed with a lag phase that represents aggregation. Full article

Hyaluronic acid (HA) is a key component of synovial fluid as it plays a crucial role in joint physiology. Its biological activity is influenced by molecular weight, local concentration, and persistence in joints. High-molecular-weight HA has a consolidated history of clinical use, whereas little is known about the metabolic effect of low-molecular-weight hyaluronate on cartilage differentiation. This study explores the potential of HA-based nanoparticles (NPs) on chondrocytes differentiation in vitro. Starting from 25 kDa and 250 kDa sodium hyaluronate solutions, two types of NPs were prepared by antisolvent precipitation in ethanol. The resulting NPs were dried in the presence of dipalmitoyl phosphatidylcholine, a natural synovial fluid component, then applied on an in vitro model of horse articular chondrocytes: no toxicity was observed and NPs prepared from 250 kDa HA promoted chondrocyte differentiation to a larger extent with respect to corresponding HA solutions, as evidenced by increased gene expression of chondrogenic markers (Col2a1 and Sox9) and reduced expression of dedifferentiation markers (Col1a1 and Runx2). These findings suggest that HA-based NPs are more effective at promoting the cellular internalization of the molecule and the differentiation of chondrocytes in vitro and could be a promising platform for drug delivery and cartilage repair. Full article

This study investigated the valorization of Ilex guayusa leaves by producing a low-caffeine, antioxidant-rich product through the supercritical antisolvent extraction (SAE) process. The objective was to concentrate the antioxidants while selectively reducing the caffeine. The SAE treatments were conducted using an ethanolic extract of guayusa leaves under varying pressure (80 bar–150 bar) and temperature (35–45 °C) conditions to improve the recovery of chlorogenic acid (CGA) and caffeine fractionation. The co-precipitation of antioxidants with polyvinylpyrrolidone (PVP) (ratio 1:1–1:2 mass/mass) as an encapsulant was also studied. The SAE precipitates were analyzed for their recovery yield, CGA and caffeine contents, antioxidant activity, and total phenols. Based on the statistical analysis, the optimal conditions for the SAE were 120 bar and 45 °C. Under these conditions, the CGA concentration increased from 43.02 mg/g extract to 237 mg/g precipitate, while the caffeine was reduced to less than 1% mass. Co-precipitation with PVP improved the recovery yield by more than two times than the SAE alone while maintaining the caffeine content below 1% mass. Additionally, the co-precipitation with PVP facilitated the formation of spherical microparticles, indicating successful encapsulation of the bioactive compounds, with an IC₅₀ of 0.51 ± 0.01 mg/mL for DPPH and 0.18 ± 0.01 mg/mL for ABTS. These results highlight the effectiveness of the SAE co-precipitation process in developing low-caffeine functional ingredients with potential food and pharmaceutical applications. Full article

Global warming has recently intensified research interest in renewable polymer chemistry, with significant attention directed towards lignin nanoparticle (LNP) synthesis. Despite progress, LNP industrial application faces challenges: (1) reliance on kraft lignin from declining raw biomass processes, (2) sulfur-rich and condensed lignin use, (3) complex lignin macroparticles to LNP conversion, using harmful and toxic solvents, and, above all, (4) lack of control over the LNP production process (i.e., anti-solvent precipitation parameters), resulting in excessive variability in properties. In this work, eco-friendly LNPs with tailored properties were produced from a semi-industrial organosolv process by studying anti-solvent precipitation variables. Using first a parametric and then a Fractional Factorial Design, predictions of LNP sizes and size distribution, as well as zeta-potential, were derived from a model over beech by-products organosolv lignin, depending on initial lignin concentration (x₁, g/L), solvent flow rate (x₂, mL/min), antisolvent composition (x₃, H2O/EtOH v/v), antisolvent ratio (x₄, solvent/antisolvent v/v), and antisolvent stirring speed (x₅, rpm). This novel chemical engineering approach holds promise for overcoming the challenges inherent in industrial lignin nanoparticle production, thereby accelerating the valorization of lignin biopolymers for high value-added applications such as cosmetics (sunscreen or emulsion) and medicine (encapsulation, nanocarriers), a process currently constrained by significant limitations. Full article

Fucoidan, a sulphated polysaccharide from brown seaweed composed of several monosaccharides, has been stated to have several bioactive properties such as antioxidant, antiviral, anticancer, antithrombic, anti-inflammatory, and immunomodulatory effects. This paper provides research findings on green extraction methods, structural analysis of fucoidan, and its associated bioactivities. Fucoidans from brown seaweeds, Fucus vesiculosus and Ascophyllum nodosum, were extracted using green solvents such as citric acid (CA) followed by MWCO (molecular weight cut-off) filtration to obtain high-purity polysaccharides. The presence of functional groups typical to fucoidans, namely, fucose, sulfate, and glycosidic bonds, in the extracts were confirmed through the data obtained from FTIR (Fourier-transform infrared spectroscopy), TGA (thermogravimetric analysis), DSC (differential scanning calorimetry), and solid-state CP–MAS (cross-polarization magic angle spinning) analysis. The MWCO analysis identified that the >300 kDa fraction can have better content of fucoidan (FV-CA 79.16%, FV-HCl 63.59%, AN-CA 79.21%, AN-HCl 80.70%) than the conventional extraction process. Furthermore, the >300 kDa fraction showed significantly higher antioxidant activities compared to crude fucoidan extracts. Crude fucoidan extracts showed significant inhibition of cell viability in human lung (A459 lung carcinoma cells) and colorectal adenocarcinoma (Caco-2) cells at higher concentrations. The fucoidan extracted with green solvents and avoiding alcohol-based precipitation has substantial antioxidant/antitumor action, so, due to this activity, it can be employed as functional foods in food applications. Full article